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STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer
SCL/TAL1 Interrupting locus (STIL) is a ciliary-related gene involved in regulating the cell cycle and duplication of centrioles in dividing cells. STIL has been found disordered in multiple cancers and driven carcinogenesis. However, the molecular mechanisms and biological functions of STIL in canc...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826476/ https://www.ncbi.nlm.nih.gov/pubmed/35155425 http://dx.doi.org/10.3389/fcell.2022.804419 |
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author | Li, Jingxian Yang, Zikun Qi, Yuanjiong Liu, Xun Liu, Yang Gao, Xinyu Li, Shuai Zhu, Jianqiang Zhang, Changwen Du, E Zhang, Zhihong |
author_facet | Li, Jingxian Yang, Zikun Qi, Yuanjiong Liu, Xun Liu, Yang Gao, Xinyu Li, Shuai Zhu, Jianqiang Zhang, Changwen Du, E Zhang, Zhihong |
author_sort | Li, Jingxian |
collection | PubMed |
description | SCL/TAL1 Interrupting locus (STIL) is a ciliary-related gene involved in regulating the cell cycle and duplication of centrioles in dividing cells. STIL has been found disordered in multiple cancers and driven carcinogenesis. However, the molecular mechanisms and biological functions of STIL in cancers remain ambiguous. Here, we systematically analyzed the genetic alterations, molecular mechanisms, and clinical relevance of STIL across >10,000 samples representing 33 cancer types in The Cancer Genome Atlas (TCGA) dataset. We found that STIL expression is up-regulated in most cancer types compared with their adjacent normal tissues. The expression dysregulation of STIL was affected by copy number variation, mutation, and DNA methylation. High STIL expression was associated with worse outcomes and promoted the progression of cancers. Gene Ontology (GO) enrichment analysis and Gene Set Variation Analysis (GSVA) further revealed that STIL is involved in cell cycle progression, Mitotic spindle, G2M checkpoint, and E2F targets pathways across cancer types. STIL expression was negatively correlated with multiple genes taking part in ciliogenesis and was positively correlated with several genes which participated with centrosomal duplication or cilia degradation. Moreover, STIL silencing could promote primary cilia formation and inhibit cell cycle protein expression in prostate and kidney cancer cell lines. The phenotype and protein expression alteration due to STIL silencing could be reversed by IFT88 silencing in cancer cells. These results revealed that STIL could regulate the cell cycle through primary cilia in tumor cells. In summary, our results revealed the importance of STIL in cancers. Targeting STIL might be a novel therapeutic approach for cancers. |
format | Online Article Text |
id | pubmed-8826476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88264762022-02-10 STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer Li, Jingxian Yang, Zikun Qi, Yuanjiong Liu, Xun Liu, Yang Gao, Xinyu Li, Shuai Zhu, Jianqiang Zhang, Changwen Du, E Zhang, Zhihong Front Cell Dev Biol Cell and Developmental Biology SCL/TAL1 Interrupting locus (STIL) is a ciliary-related gene involved in regulating the cell cycle and duplication of centrioles in dividing cells. STIL has been found disordered in multiple cancers and driven carcinogenesis. However, the molecular mechanisms and biological functions of STIL in cancers remain ambiguous. Here, we systematically analyzed the genetic alterations, molecular mechanisms, and clinical relevance of STIL across >10,000 samples representing 33 cancer types in The Cancer Genome Atlas (TCGA) dataset. We found that STIL expression is up-regulated in most cancer types compared with their adjacent normal tissues. The expression dysregulation of STIL was affected by copy number variation, mutation, and DNA methylation. High STIL expression was associated with worse outcomes and promoted the progression of cancers. Gene Ontology (GO) enrichment analysis and Gene Set Variation Analysis (GSVA) further revealed that STIL is involved in cell cycle progression, Mitotic spindle, G2M checkpoint, and E2F targets pathways across cancer types. STIL expression was negatively correlated with multiple genes taking part in ciliogenesis and was positively correlated with several genes which participated with centrosomal duplication or cilia degradation. Moreover, STIL silencing could promote primary cilia formation and inhibit cell cycle protein expression in prostate and kidney cancer cell lines. The phenotype and protein expression alteration due to STIL silencing could be reversed by IFT88 silencing in cancer cells. These results revealed that STIL could regulate the cell cycle through primary cilia in tumor cells. In summary, our results revealed the importance of STIL in cancers. Targeting STIL might be a novel therapeutic approach for cancers. Frontiers Media S.A. 2022-01-26 /pmc/articles/PMC8826476/ /pubmed/35155425 http://dx.doi.org/10.3389/fcell.2022.804419 Text en Copyright © 2022 Li, Yang, Qi, Liu, Liu, Gao, Li, Zhu, Zhang, Du and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Li, Jingxian Yang, Zikun Qi, Yuanjiong Liu, Xun Liu, Yang Gao, Xinyu Li, Shuai Zhu, Jianqiang Zhang, Changwen Du, E Zhang, Zhihong STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer |
title | STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer |
title_full | STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer |
title_fullStr | STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer |
title_full_unstemmed | STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer |
title_short | STIL Acts as an Oncogenetic Driver in a Primary Cilia-Dependent Manner in Human Cancer |
title_sort | stil acts as an oncogenetic driver in a primary cilia-dependent manner in human cancer |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826476/ https://www.ncbi.nlm.nih.gov/pubmed/35155425 http://dx.doi.org/10.3389/fcell.2022.804419 |
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